1. Field of the Invention
This invention relates to 2-amino-6,7-dihydroxy-4-thiaheptanoic acid derivatives, which are useful as therapeutic agents in the treatment of leukocytopenia resulting from various causes such as, diseases due to decrease of leukocytes, diseases requiring, from the therapeutic viewpoint an, increase of bone marrow cells or leukocytes, thrombocytopenia caused by various reasons, diseases due to decrease of thrombocyte, or diseases requiring, from the therapeutic viewpoint, increase of thrombocyte.
2. Description of Related Art
In Hoppe-Seyler's Zeitschrift fur Physiologiche Chemie 364, pp 593-606 (1983), a synthetic peptide derived from lipoprotein produced by E. coli, which is shown by the formula: ##STR2## is disclosed.
And, in JPA H4(1992)-046194, WS 1279A substance shown by the formula: ##STR3## is disclosed.
Achiwa et al. synthesized these compounds as optical active compounds. [cf. JPA H4(1992)-099796, Chem. Pharm. Bull. 39, p 2590 (1991) and Peptide Chemistry, p. 361 (1991)].
However, the compounds of this invention are not described in these references.
Incidentally, abbreviations of amino acid, peptide or the like used in the present invention are based on those in accordance with IUPAC-IUB Commission on Biochemical Nomenclature or those conventionally used in the relevant fields, and, possible optical isomers of amino acid are, unless otherwise specified, L-isomers.
Chemotherapy or radiotherapy of cancers causes serious leukocytopenia or serious thromobocytopenia. The former induces a lowering of resistance against infections or other various diseases so that sufficient therapeutic effects are not expected. The latter induces insufficiency of a hemostatic mechanism so that sufficient therapeutic effects are not expected. These are being taken up as a grave concern in the field of cancer therapy. Under such circumstances, development of drugs, which mitigate the suppression of hematopoietic function caused by these therapeutic methods and are capable of promoting the recovery of leukocyte number or thrombocyte number, has been ardently desired. Further, in the therapy by bone marrow transplantation, drugs capable of promoting the proliferation of bone marrow cells then transplanted and capable of recovering the number of leukocyte promptly are desired. Furthermore, these drugs can be used for therapeutic agents of thrombocytopenia after bone marrow transplantation or autoimmunodisease accompanied by thombocytopenia, such as a plastic anemia and paroxymal thrombocytopenic purpura.
While taking the present circumstances mentioned above into consideration, the present inventors pursued their studies, from a fresh viewpoint, on compounds having the action of increasing the number of leukocytes. As the result, the present inventors found that the novel 2-amino-6,7-dihydroxy-4-thiaheptanoic acid derivatives of this invention promote the proliferation of bone marrow cells of mice and increase the number of peripheral leukocytes. Further, said compounds also stimulate bone marrow cells of mice so as to promote proliferation and differentiation of megakaryocytes. Based on these findings, the present inventors made further studies to complete the present invention.